COMET lights up epigenetic regulation

Nature Chemical Biology

March 15, 2016

A new technique for highly precise control of gene expression in human cells is reported in a study published online this week in Nature Chemical Biology. This study demonstrates the ability to control the activity of a class of enzymes involved in gene expression using inhibitors designed to switch on only when exposed to a specific type of light, providing the first major tool in the field of optoepigenetics.

The field of optogenetics enables control of cellular behavior and biological function in the presence of light at a particular location, time and dose. However, the ability to control enzymes that modulate gene expression has remained elusive.

In this study, Stephen Haggarty, Ralph Mazitschek and colleagues devised a method called chemo-optical modulation of epigenetically regulated transcription (COMET) that blocks the action of histone deacetylases (HDACs), a class of enzymes critical to DNA transcription, using small-molecule HDAC inhibitors that switch on or off with light exposure. They show that applying blue light results in the loss of HDAC activity and corresponding changes to the regulation of DNA transcription, while the removal of light undoes these changes. The authors demonstrate the rapid modulation of gene expression with repeated regimens of light exposure. They note that using light to alter the activity of an enzyme involved in gene regulation could represent a new approach for treating disorders characterized by impaired epigenetic regulation, such as neurodegeneration and some cancers.